BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

Objective To investigate the association between cardiovascular autonomic function and voiding symptoms in Parkinson disease(PD)patients.Methods We reviewed PD patients from the Department of Neurology of Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)between November 2020 and July 2023.Patients with PD were diagnosed by movement disorder specialists and received motor symptoms assessment based on Movement Disorders Society-Unified Parkinson's Disease Rating Scale part Ⅲ(MDS-UPDRS Ⅲ).We included those patients who underwent 24-hour ambulatory blood pressure monitoring(ABPM),ultrasound measured post void residual(PVR)and uroflowmetry.Subjects were divided into two groups:PD patients with nocturnal hypertension(PD-NH)group and PD patients without nocturnal hypertension(PD-nNH)group,according to the average nocturnal blood pressure.General clinical features,clinical assessments and urinary evaluations were compared between the two groups.We calculated average real variability(ARV)and examined its correlation factors using generalized linear models.Results Among the total of 87 PD patients,46(52.87% )were found to have nocturnal hypertension(NH).The PD-NH group exhibited more PVR[1.00(0.00,21.25)mL]compared to the PD-nNH group[0.00(0.00,5.50)mL](P<0.05).Additionally,generalized linear model analysis which scale response is Gamma with log link showed in PD patients,ARV of 24-hour diastolic blood pressure was correlated with PVR(OR=1.003,95% CI:1.001-1.005,P=0.008)and sex(male,OR=1.234,95% CI:1.050-1.451,P=0.011).Conclusion Our study demonstrates the association between cardiovascular autonomic function and voiding symptoms in PD.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin’s lymphoma Berlin–Frankfurt–Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. Conclusion This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Background Imidacloprid is a neonicotinoid insecticide that is widely used in agricultural production, with a high detection rate in human biological samples. Previous studies have shown a high correlation between imidacloprid exposure and liver injury, but the specific mechanism is still unknown. Objective To observe potential toxic effects of HepG2 cells and its perturbation of non-targeted metabolic profile after imidacloprid exposure, and to explore possible molecular mechanisms of hepatotoxicity of imidacloprid by analyzing invovlved biological processes and signaling pathways. Methods HepG2 cell suspension was prepared and seeded in a 96-well plate, which was divided into blank control group, dimethyl sulfoxide (DMSO) solvent control group and imidacloprid exposure groups with multiple concentrations. Each group was set with 5 parallel samples. The viability of HepG2 cells viability were determined after 8 h of exposure to different concentrationsof imidacloprid (1, 2.5, 5, 7.5, 10 mmol·L⁻¹), and the dose-effect relationship was analyzed. A proper concentration (3 mmol·L⁻¹ with 80% viability) was chosen for imidacloprid exposure, non-targeted metabolomic analysis was applied to the cultivated HepG2 cells using UHPLC-Q-TOF/MS technology, the differential metabolites between groups were screened, and the bioprocess and related signaling pathways of their enrichment were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results Compared to the other two groups, the survival rates of HepG2 cells in the imidacloprid exposure groups decreased. A survival rate of about 86% of HepG2 cells was found in HepG2 cells exposed to 2.5 mmol·L⁻¹ imidacloprid exposure. The non-targeted metabolomics studies showed that 61 metabolites were significantly affected in HepG2 cells after 3 mmol·L⁻¹ imidacloprid exposure, including creatine (variable importance in projection VIP=1.11, P<0.001), arginine (VIP=1.47, P=0.048), taurine (VIP=4.28, P=0.001), and α-D-glucose (VIP=1.90, P=0.006). The differential metabolites enriched in bioprocess and related signaling pathways were mainly directed to mTOR signaling pathways (P<0.001), arginine and proline metabolism (P=0.002), and galactose metabolism (P=0.015). Conclusion Imidacloprid exposure can significantly inhibit the survival rate of HepG2 cells, and interfere with the mTOR signaling pathway, arginine and proline metabolism, galactose metabolism, and so on.

Depression is a mental disorder with high morbidity, disability and relapse rates. Ginkgo biloba extract (GBE), a traditional Chinese medicine, has a long history of clinical application in the treatment of cerebral and mental disorders, but the key mechanism remains incompletely understood. Here we showed that GEB exerted anti-depressant effect in mice through regulating gut microbial metabolism. GBE protected against unpredictable mild stress (UMS)-induced despair, anxiety-like and social avoidance behavior in mice without sufficient brain distribution. Fecal microbiome transplantation transmitted, while antibiotic cocktail abrogated the protective effect of GBE. Spatiotemporal bacterial profiling and metabolomics assay revealed a potential involvement of Parasutterella excrementihominis and the bile acid metabolite ursodeoxycholic acid (UDCA) in the effect of GBE. UDCA administration induced depression-like behavior in mice. Together, these findings suggest that GBE acts on gut microbiome-modulated bile acid metabolism to alleviate stress-induced depression.
Humans ; Mice ; Animals ; Depression/drug therapy* ; Gastrointestinal Microbiome ; Plant Extracts ; Ginkgo biloba

Objective:To investigate and analyze the allocation status of oral health resources in Yunnan Province at the end of the 13th Five-Year Plan, providing a scientific basis for the rational resource allocation and formulation regional oral health plan for government health administrative departments.Methods:With the method of general survey, a cross-sectional study was conducted to investigate the allocation of material and human resources of all kinds of stomatological medical institutions registered in the health administrative departments in Yunnan before January 1, 2020. The general situation of oral health resources was analyzed by descriptive statistical analysis.Results:There were 2 712 stomatological medical institutions in Yunnan, 634 public and 2 078 non-public included. The largest number was in Kunming (1 167) and the least in Diqing (19). There were 9 018 dental chairs in total, among which 2 584 in public and 6 434 in non-public. Kunming had the largest number of chairs (3 612) and Nujiang had the least (57). There were 702 oral and maxillofacial surgical beds, all of which were distributed in public. There were 15 148 stomatological personnel, including 3 667 in public and 11 481 in non-public. The average ratio of stomatologist to population was 1∶6 615. Dehong (1∶6 620) was close to this average level, while Kunming (1∶2 283) and Yuxi (1∶4 936) were lower than the average and the other 13 states (cities) were higher. The population ratio of licensed stomatologist was only 1∶9 110. The average ratio of stomatologist to nurses was 1∶0.94. Honghe (1∶1.05), Kunming (1∶1.00), Yuxi (1∶1.18) and Qujing (1∶0.94) was better than or reached the average level, while the other 13 states (cities) were lower than this average. And this ratio in public comprehensive medical institutions was only 1∶0.38.Conclusions:The distribution of oral health resources in Yunnan was unbalanced between public and non-public institutions and among states (cities), mainly distributed in economically developed states (cities) and non-public institutions. For the oral health in Yunnan Province, the workforce was insufficient and the structure was unreasonable, and the proportion of nurses was seriously insufficient in public comprehensive medical institutions.

Objective:To explore the effect of collaborative teaching on anesthesia nursing.Methods:A total of 50 anesthesiology nursing undergraduates were randomly selected from the Batch 2018 of Harbin Medical University as experimental group and control group respectively. The two groups completed the teaching tasks in the same teaching hours. The control group was taught by traditional teaching method. The experimental group was jointly taught by the teaching team composed of anesthesia nursing teachers, humanistic medicine teachers and ideological and political teachers. After the completion of teaching, the two groups of students were surveyed by questionnaire to evaluate the teaching effect. SPSS 22.0 was used Fisher's exact probability test.Results:The questionnaire results showed that in the evaluation of collaborative teaching, the evaluation of expanded ideological, political and humanistic knowledge (96.00%, 48/50), strengthened the understanding of theoretical knowledge (88.00%, 44/50), improved doctor-patient communication ability (90.00%, 45/50), improved clinical strain ability (94.00%, 47/50), and improved professional identity (86.00%, 43/50) of the experimental group was significantly higher than that of the control group ( P<0.05). Conclusion:The collaborative teaching method in anesthesiology nursing course can not only strengthen students' mastery of clinical skills, but also cultivate lofty sense of mission and professional spirit, strengthen doctors' benevolent belief, improve medical students' comprehensive quality in an all-round way, and promote the development of new medical education.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

AlM: To investigate the effect of C. sinensis extracts on HBx (Hepatitis B virus X protein) induced cell proliferation and extracellular matrix (ECM) accumulation and the underlying mechanism in cultured human mesangial cells (HMCs). METHODS: Human mesangial cells were stable transfected with pCMV-HBx to establish an HBx over-expression model, and a control group was transfected with an empty vector. Cell proliferation was determined by MTT assay and DNA synthesis assay. Western blotting was used to measure the expression of PI3K/Akt signaling pathway-related proteins and extracellular matrix. RESULTS: HBx transfection induced cell proliferation, matrix accumulation. HBx-transfected mesangial cells had increased activity of the PI3K/Akt pathways, and treatment with C. sinensis suppressed this effect. CONCLUSlON: C.sinensis attenuates the HBx-induced human mesangial cell proliferation and matrix production in human mesangial cells via inhibition of the PI3K/Akt pathways.

Background Atmospheric fine particulate matter (PM_2.5) can induce abnormal early embryo development, resulting in adverse pregnancy outcomes such as embryo damage and spontaneous abortion. The vascular remodeling of maternal-fetal interface regulated by hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) axis is a key link in early embryo development. Objective To investigate the effects of pre-pregnancy PM_2.5 exposure on the uterine state of mice before conception and the vascular remodeling of maternal-fetal interface after conception, and to further explore the regulatory role of the HIF-1α/VEGF axis. Methods Forty eight-week-old C57BL/6J sexually mature female mice and several males (for mating, without any treatment) were adaptive fed for 1 week. The female mice were divided into a PM_2.5 exposure group and a control group, 20 mice per group. The PM_2.5 exposure group was given 3 mg·kg⁻¹ PM_2.5 suspension by nasal instillation, once every other day for four weeks; the control group were treated with the same dose of blank sampling membrane suspension. Body weight of the mice was recorded every week during the experimental period. At the end of the exposure, six mice from each group were sacrificed. Then the uterus was weighted and its organ coefficients were calculated, a histopathological morphology evaluation was conducted by HE staining, and the mRNA expressions of HIF-1α, VEGF and its receptors Flt-1 and Flk-1 in the uterus samples were further examined. The remaining 14 female mice in each group were caged with male mice overnight with a sex ratio of 2:1, then we calculated the pregnancy rate. On gestation day 10 (GD10), the female mice were decapitated and the uterus was dissected, the histopathological morphology of embryo and placenta were observed by HE staining, and the mRNA expressions of HIF-1α, VEGF and its receptors Flt-1 and Flk-1 were detected as well in the uterus samples. Results Compared with the control group, the pre-pregnancy PM_2.5 exposure had no significant effect on body weight gain of the female mice, but decreased uterine organ coefficient, accompanied by pathological damage such as endometrium thinning as well as decreased mRNA expressions of HIF-1α, VEGF and its receptors Flt-1 and Flk-1 (all Ps<0.05). After mating, the pre-pregnancy PM_2.5 exposure induced a decrease of the pregnancy rate (control group: 9/14; exposure group: 5/14) and abnormal embryo arrangement, small placenta, narrowing of spiral arteries (control group: 1.00±0.06; exposure group: 0.86±0.08; P=0.01), as well as significant decreases in HIF-1α, VEGF and its receptor Flk-1 mRNA expressions. (all Ps <0.05). Conclusion Pre-pregnancy PM_2.5 exposure has adverse effects on the pathological structure and angiogenesis in female mice uterus, leading to abnormal vascular network remodeling at the mother-fetal interface after conception, and the HIF-1α/VEGF axis may play a regulatory role.